UBE2E3 p.Gln44Arg

Variant names:

• chr2-180982173-A-G
• rs746491983
• NM_006357.4:c.131A>G
• UBE2E3 p.Gln44Arg

Your query was ambiguous. Multiple possible variants found:

• chr2-180982173-A-G
• chr2-180982173-AG-GT
• chr2-180982173-AG-GC
• chr2-180982173-AG-GA
• chr2-180982172-CAG-AGA
• chr2-180982172-CA-AG

Variant summary

Our verdict is

Uncertain significance

0 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006357.4(UBE2E3):​c.131A>G​(p.Gln44Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBE2E3 NM_006357.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.37
• Publications: 0 publications found

Genes affected

UBE2E3 (HGNC:12479): (ubiquitin conjugating enzyme E2 E3) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. The encoded protein shares 100% sequence identity with the mouse and rat counterparts, which indicates that this enzyme is highly conserved in eukaryotes. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.112).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006357.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2E3	NM_006357.4	MANE Select	c.131A>G	p.Gln44Arg	missense	Exon 2 of 6	NP_006348.1	Q969T4
	UBE2E3	NM_001278554.2		c.131A>G	p.Gln44Arg	missense	Exon 2 of 6	NP_001265483.1	Q969T4
	UBE2E3	NM_001278555.2		c.131A>G	p.Gln44Arg	missense	Exon 2 of 6	NP_001265484.1	Q969T4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2E3	ENST00000410062.9	TSL:1 MANE Select	c.131A>G	p.Gln44Arg	missense	Exon 2 of 6	ENSP00000386788.3	Q969T4
	UBE2E3	ENST00000602710.5	TSL:1	c.131A>G	p.Gln44Arg	missense	Exon 2 of 6	ENSP00000473623.1	Q969T4
	UBE2E3	ENST00000888071.1		c.131A>G	p.Gln44Arg	missense	Exon 2 of 7	ENSP00000558130.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.011	T
Eigen	Benign	0.020
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		6.4
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.11
Sift	Benign	0.60	T
Sift4G	Benign	0.51	T
PromoterAI		0.0075	Neutral
Varity_R		0.14
gMVP		0.54
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs746491983;

hg19: chr2-181846900;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline